In a delicately tuned network, which is the current concept of the immune system, both self (or altered-self) and non-self reactions are normally being generated. An aging immune system displays increased vulnerability to disease or what seems to be an evolving discord or 'untuning' of the system. Study of the aging immune system would reveal not only important information about the mechanism of aging, but also new information concerning those functions of the immune system not yet clearly elucidated. One such area, i.e., early events occurring in the immune response and, in particular, how antigen reacts with the immune system, has been made the focus of this proposal. NIA 'colony' Fischer 344 male rats, when immunized with bovine serum albumin (BSA), have shown an age-related decline in humoral immune response as measured by the Farr ABC assay. Other findings include fewer SRBC rosettes with hepatocytes and less 3H-aniline-azo-BSA uptake in the liver tissue of older individuals. These results suggest the involvement of antigen recognition and processing stages and may support another current concept of immunoregulation, in which hepatic function is implicated. Receptor recognition, antigen binding to cell surfaces, antigen uptake and subsequent processing, will be studied by the use of rosetting, labelled lectins and antigens, conjugated fluorescein immunoreagents, and nucleotide incoroporation. These investigations will focus on autologous cellular reactions among liver cells (parenchymal and nonparenchymal) and between these cells and autologous or allogeneic cells of the lymphoid system. The handling of isologous serum albumin (RSA) will be assayed by the Farr ABC test and by biological and chemical characterization of antigen metabolites to further assess the aging humoral responses, and antigen processing and tolerance. In the plan of study, the liver may be regarded as the interface between external influences on the immune system and products of the immune system itself, and thus information will be gained about the imbalance in reactions of self-non-self that tend to be characteristic of aging.